Mathematical modelling supports the existence of a threshold hydrogen concentration and media-dependent yields in the growth of a reductive acetogen

Abstract

The bacterial production of acetate via reductive acetogenesis along the Wood-Ljungdahl metabolic pathway is an important source of this molecule in several environments, ranging from industrial bioreactors to the human gastrointestinal tract. Here, we contributed to the study of reductive acetogens by considering mathematical modelling techniques for the prediction of bacterial growth and acetate production. We found that the incorporation of a hydrogen uptake concentration threshold into the models improves their predictions and we calculated this threshold as 86.2 mM (95% confidence interval 6.1-132.6 mM). Monod kinetics and first-order kinetics models, with the inclusion of two candidate threshold terms or reversible Michaelis-Menten kinetics, were compared to experimental data and the optimal formulation for predicting both growth and metabolism was found. The models were then used to compare the efficacy of two growth media for acetogens. We found that the recently described general acetogen medium was superior to the DSMZ medium in terms of unbiased estimation of acetogen growth and investigated the contribution of yeast extract concentration to acetate production and bacterial growth in culture. The models and their predictions will be useful to those studying both industrially and environmentally relevant reductive acetogenesis and allow for straightforward adaptation to similar cases with different organisms.

Faster Growth Enhances Low Carbon Fuel and Chemical Production Through Gas Fermentation

“…Exploring the physiological boundaries of acetogens has been informative for understanding regulation of their energy-limited metabolism ( Valgepea et al, 2017a ; Klask et al, 2020 ; Mahamkali et al, 2020 ; Jin et al, 2021 ). Additionally, various bioprocess approaches, multi-omics analysis, construction of metabolic models, and development of genetic tools are being pursued for development of cell factories with enhanced substrate conversion, product distribution, and expanded product spectrum ( Valgepea et al, 2018 ; Lemgruber et al, 2019 ; Molitor et al, 2019 ; Heffernan et al, 2020 ; Smith et al, 2020 ; Bourgade et al, 2021 ; Diender et al, 2021 ; Fackler et al, 2021 ; Jin et al, 2021 ; Pavan et al, 2022 ). Notably, the effects of μ on acetogen metabolism and the gas fermentation bioprocess have not been established.…”

Systems biology illuminates alternative metabolic niches in the human gut microbiome

“…The presence of these reactions allowed the model to draw on an effectively unlimited source of acetyl-CoA from CO 2 and H 2 . Regardless of whether the previous annotation of this pathway (which has not been biochemically validated) is correct, reductive acetogenesis may not be thermodynamically favorable during in vitro growth in our anaerobic chamber, where the H 2 concentration is ≤ 5% (Smith et al, 2020). Blocking model flux through the carbon monoxide dehydrogenase reaction of this pathway increased growth dependency on uptake of both arginine and acetate, reflecting our experimental observations (Figure 3C).…”

Systems biology elucidates the distinctive metabolic niche filled by the human gut microbe Eggerthella lenta

“…The presence of these reactions allowed the model to draw on an effectively unlimited source of acetyl-CoA from CO 2 and H 2 . Regardless of whether the previous annotation of this pathway (which has not been biochemically validated) is correct, reductive acetogenesis may not be thermodynamically favorable during in vitro growth in our anaerobic chamber, where the H 2 concentration is ≤5% [ 41 ]. Blocking model flux through the carbon monoxide dehydrogenase reaction of this pathway increased growth dependency on uptake of both arginine and acetate, reflecting our experimental observations ( Fig 3C ).…”